Premium
Docosahexaenoic Acid (DHA), not Leucine, May Protect HepG2 Cells from Palmitate‐Induced Non‐Alcoholic Fatty Liver Disease
Author(s) -
Baum Jamie I,
Carroll Timothy G,
Shouse Stephanie A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1036.7
Subject(s) - docosahexaenoic acid , fatty liver , insulin resistance , medicine , leucine , endocrinology , steatosis , steatohepatitis , lipid metabolism , type 2 diabetes , polyunsaturated fatty acid , diabetes mellitus , chemistry , fatty acid , biochemistry , disease , amino acid
Non‐alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States, affecting 70 million adults and ~3% of young children. NAFLD is characterized by an accumulation of fat in the liver cells that is not caused by alcohol. NAFLD is closely associated with obesity and insulin resistance, which are precursors for development of type 2 diabetes. Recent data suggests that the PPARs (PPARα and PPARγ may be connected to the development and progression of NAFLD, which make them potential biomarkers for treating and diagnosing NAFLD. Currently, there are several approaches to treating NAFLD, including nutrition therapy and specific food recommendations. Diets high in protein, high in the branched‐chain amino acid leucine, and diets high in polyunsaturated fatty acids, such as DHA, have been linked with weight reduction and improved insulin resistance. However, neither has been evaluated as a treatment for NAFLD. Therefore, the objective of this study was to analyze the ability of leucine and DHA to act either synergistically or alone to reduce markers of NAFLD using HepG2 cells treated with palmitate as an in vitro model. HepG2 cells (80% confluent) received one of 6 treatments for 48 hours: control, vector control, 0.75 mM palmitate, 5 mM leucine + palmitate, 0.1 mM DHA + palmitate, or leucine + DHA + palmitate. Lipid deposition and markers of energy metabolism were measured. Data was analyzed using one‐way ANOVA with P < 0.05 indicating significance. There was no effect of leucine on cellular lipid deposition. However, cells treated with DHA had significantly less lipid deposition compared to cells treated with palmitate or palmitate + leucine. Palmitate increased Tfam expression compared to controls, however, there was no further effect of leucine. Palmitate + DHA and palmitate + leucine + DHA significantly increased Tfam expression compared to control, palmitate and palmitate + leucine. Palmitate significantly lowered PGC1a and PPARg expression, however treatment with DHA further decreased PGC1α and PPARγ compared to controls and palmitate, alone. Preliminary data shows no treatment effect on SIRT1 or mTOR phosphorylation. Taken together, these data suggest that DHA, not leucine, has the potential to reduce markers of NAFLD in HepG2 cells. Support or Funding Information Arkansas Biosciences Institute. University of Arkansas State Undergraduate Research Fellowship.